CA2451643A1 - Antisense modulation of superoxide dismutase 1, soluble expression - Google Patents

Antisense modulation of superoxide dismutase 1, soluble expression Download PDF

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Publication number
CA2451643A1
CA2451643A1 CA002451643A CA2451643A CA2451643A1 CA 2451643 A1 CA2451643 A1 CA 2451643A1 CA 002451643 A CA002451643 A CA 002451643A CA 2451643 A CA2451643 A CA 2451643A CA 2451643 A1 CA2451643 A1 CA 2451643A1
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compound
soluble
superoxide dismutase
antisense oligonucleotide
expression
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CA002451643A
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CA2451643C (en
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C. Frank Bennett
Kenneth Dobie
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Biogen MA Inc
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    • C—CHEMISTRY; METALLURGY
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    • C12N15/00—Mutation or genetic engineering; DNA or RNA concerning genetic engineering, vectors, e.g. plasmids, or their isolation, preparation or purification; Use of hosts therefor
    • C12N15/09—Recombinant DNA-technology
    • C12N15/11—DNA or RNA fragments; Modified forms thereof; Non-coding nucleic acids having a biological activity
    • C12N15/113—Non-coding nucleic acids modulating the expression of genes, e.g. antisense oligonucleotides; Antisense DNA or RNA; Triplex- forming oligonucleotides; Catalytic nucleic acids, e.g. ribozymes; Nucleic acids used in co-suppression or gene silencing
    • C12N15/1137—Non-coding nucleic acids modulating the expression of genes, e.g. antisense oligonucleotides; Antisense DNA or RNA; Triplex- forming oligonucleotides; Catalytic nucleic acids, e.g. ribozymes; Nucleic acids used in co-suppression or gene silencing against enzymes
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P21/00—Drugs for disorders of the muscular or neuromuscular system
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00—Drugs for disorders of the nervous system
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    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12Y—ENZYMES
    • C12Y115/00—Oxidoreductases acting on superoxide as acceptor (1.15)
    • C12Y115/01—Oxidoreductases acting on superoxide as acceptor (1.15) with NAD or NADP as acceptor (1.15.1)
    • C12Y115/01001—Superoxide dismutase (1.15.1.1)
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K38/00—Medicinal preparations containing peptides
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    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
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    • C12N2310/00—Structure or type of the nucleic acid
    • C12N2310/10—Type of nucleic acid
    • C12N2310/11—Antisense
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N2310/00—Structure or type of the nucleic acid
    • C12N2310/30—Chemical structure
    • C12N2310/31—Chemical structure of the backbone
    • C12N2310/315—Phosphorothioates
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
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    • C12N2310/00—Structure or type of the nucleic acid
    • C12N2310/30—Chemical structure
    • C12N2310/32—Chemical structure of the sugar
    • C12N2310/321—2'-O-R Modification
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
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    • C12N2310/00—Structure or type of the nucleic acid
    • C12N2310/30—Chemical structure
    • C12N2310/33—Chemical structure of the base
    • C12N2310/334—Modified C
    • C12N2310/3341—5-Methylcytosine
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
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    • C12N2310/00—Structure or type of the nucleic acid
    • C12N2310/30—Chemical structure
    • C12N2310/34—Spatial arrangement of the modifications
    • C12N2310/341—Gapmers, i.e. of the type ===---===
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    • C12N2310/00—Structure or type of the nucleic acid
    • C12N2310/30—Chemical structure
    • C12N2310/34—Spatial arrangement of the modifications
    • C12N2310/346—Spatial arrangement of the modifications having a combination of backbone and sugar modifications
    • C—CHEMISTRY; METALLURGY
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    • C12N2310/00—Structure or type of the nucleic acid
    • C12N2310/30—Chemical structure
    • C12N2310/35—Nature of the modification
    • C12N2310/352—Nature of the modification linked to the nucleic acid via a carbon atom
    • C12N2310/3525—MOE, methoxyethoxy
    • Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
    • Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
    • Y02P—CLIMATE CHANGE MITIGATION TECHNOLOGIES IN THE PRODUCTION OR PROCESSING OF GOODS
    • Y02P20/00—Technologies relating to chemical industry
    • Y02P20/50—Improvements relating to the production of bulk chemicals
    • Y02P20/582—Recycling of unreacted starting or intermediate materials

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  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Genetics & Genomics (AREA)
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  • Bioinformatics & Cheminformatics (AREA)
  • Biomedical Technology (AREA)
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  • Public Health (AREA)
  • Animal Behavior & Ethology (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
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  • Neurology (AREA)
  • Neurosurgery (AREA)
  • Orthopedic Medicine & Surgery (AREA)
  • Physical Education & Sports Medicine (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)

Abstract

Antisense compounds, compositions and methods are provided for modulating th e expression of superoxide dismutase 1, soluble. The compositions comprise antisense compounds, particularly antisense oligonucleotides, targeted to nucleic acids encoding superoxide dismutase 1, soluble. Methods of using the se compounds for modulation of superoxyde dismutase 1, soluble expression and f or treatment of diseases associated with expression of superoxide dismutase 1, soluble are provided.

Claims (20)

1. A compound 8 to 50 nucleobases in length targeted to a nucleic acid molecule encoding human superoxide dismutase 1, soluble, wherein said compound specifically hybridizes with and inhibits the expression of human superoxide dismutase 1, soluble.
2. The compound of claim 1 is an antisense oligonucleotide.
3. The compound of claim 2 wherein the antisense oligonucleotide has a sequence comprising SEQ ID NO: 13, 15, 17, 18, 20, 22, 23, 24, 25, 27, 29, 30, 31, 32, 33, 35, 36, 37, 38, 40, 41, 42, 43, 45, 48, 52, 59, 60, 61, 67, 69, 74, 78, 80, 81, 83 or 90.
4. The compound of claim 2 wherein the antisense oligonucleotide comprises at least one modified internucleoside linkage.
5. The compound of claim 4 wherein the modified internucleoside linkage is a phosphorothioate linkage.
6. The compound of claim 2 wherein the antisense oligonucleotide comprises at least one modified sugar moiety.
7. The compound of claim 6 wherein the modified sugar moiety is a 2'-O-methoxyethyl sugar moiety.
8. The compound of claim 2 wherein the antisense oligonucleotide comprises at least one modified nucleobase.
9. The compound of claim 8 wherein the modified nucleobase is a 5-methylcytosine.
10. The compound of claim 2 wherein the antisense oligonucleotide is a chimeric oligonucleotide.
11. A compound 8 to 50 nucleobases in length which specifically hybridizes with at least an 8-nucleobase portion of an active site on a nucleic acid molecule encoding human superoxide dismutase 1, soluble.
12. A composition comprising the compound of claim 1 and a pharmaceutically acceptable carrier or diluent.
13. The composition of claim 12 further comprising a colloidal dispersion system.
14. The composition of claim 12 wherein the compound is an antisense oligonucleotide.
15. A method of inhibiting the expression of superoxide dismutase 1, soluble in human cells or tissues comprising contacting said cells or tissues with the compound of claim 1 so that expression of superoxide dismutase 1, soluble is inhibited.
16. A method of treating a human having a disease or condition associated with superoxide dismutase 1, soluble comprising administering to human a therapeutically or prophylactically effective amount of the compound of claim 1 so that expression of superoxide dismutase 1, soluble is inhibited.
17. The method of claim 16 wherein the disease or condition is amyotrophic lateral sclerosis.
18. The method of claim 16 wherein the disease or condition arises from aberrant apoptosis.
19. The method of claim 16 wherein the disease or condition is a hyperproliferative disorder.
20. The compound of claim 1 targeted to a nucleic acid molecule encoding an alternatively spliced variant of human superoxide dismutase 1, soluble, wherein said compound specifically hybridizes with and inhibits the expression of an alternatively spliced variant of human superoxide dismutase 1, soluble.
CA2451643A 2001-06-21 2002-06-19 Antisense modulation of superoxide dismutase 1, soluble expression Expired - Lifetime CA2451643C (en)

Priority Applications (1)

Application Number Priority Date Filing Date Title
CA2790034A CA2790034A1 (en) 2001-06-21 2002-06-19 Antisense modulation of superoxide dismutase 1, soluble expression

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
US88836001A 2001-06-21 2001-06-21
US09/888,360 2001-06-21
PCT/US2002/019664 WO2003000707A2 (en) 2001-06-21 2002-06-19 Antisense modulation of superoxide dismutase 1, soluble expression

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CA2790034A Division CA2790034A1 (en) 2001-06-21 2002-06-19 Antisense modulation of superoxide dismutase 1, soluble expression

Publications (2)

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CA2451643A1 true CA2451643A1 (en) 2003-01-03
CA2451643C CA2451643C (en) 2012-11-13

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CA2451643A Expired - Lifetime CA2451643C (en) 2001-06-21 2002-06-19 Antisense modulation of superoxide dismutase 1, soluble expression
CA2790034A Abandoned CA2790034A1 (en) 2001-06-21 2002-06-19 Antisense modulation of superoxide dismutase 1, soluble expression

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US (5) US7132530B2 (en)
EP (3) EP2270024B1 (en)
AU (1) AU2002315393A1 (en)
CA (2) CA2451643C (en)
HK (1) HK1147776A1 (en)
WO (1) WO2003000707A2 (en)

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